Unexpected effect of testosterone in hypergonadotropic hypogonadism and nodular Leydig cell hiperplasia. Report of one case / Efecto inesperado de la testosterona en un hipogonadismo hipergonadotrófico e hiperplasia de las células de Leydig. Informe de un caso

ABSTRACT We report a 27 -year-old male referred because of hypergonadotropic hypogonadism with low testosterone and azoospermia. At 23 years of age, he underwent an excision of a hypoechoic 0.7 cm nodule of the left testicle. The pathological diagnosis was a Leydig cell tumor. In the right testicle, there were three nodules at ultrasound, the biggest measuring 0.6 cm. Four years later, the nodules in the right testicle were still present and the larger nodule was excised. The biopsy showed tubules with only Sertoli cells in the perinodular zone. Diffuse and nodular hyperplasia of the Leydig cells was found in the interstitium. The pathological diagnosis was Sertoli syndrome with severe hyperplasia of the Leydig cells. With testosterone therapy, LH decreased, and the nodules disappeared. Thereafter, upon interrupting therapy, LH increased, and the nodules reappeared in two occasions. Resuming testosterone treatment, the nodules disappeared again, suggesting a Leydig cell hyperplasia dependent on chronic LH stimulation.

Presentamos un varón de 27 años referido por hipogonadismo hipergonadotrófico con testosterona baja y azoospermia. El paciente tenía el antecedente de un nódulo sólido hipoecogénico de 0,7 cm en el testículo izquierdo, extirpado los 23 años de edad en el año 2002 y diagnosticado patológicamente como tumor de células de Leydig. En ese año se encontraron tres nódulos en el testículo derecho por ultrasonografía, el mayor de 0,6 cm. Cuatro años después, en 2007, los micronódulos del testículo derecho seguían presentes. El mayor de ellos fue extirpado. En la biopsia, había túbulos con solo células de Sertoli en la zona perinodular. En el intersticio había hiperplasia difusa y nodular de las células de Leydig. El diagnóstico patológico fue un síndrome de Sertoli con severa hiperplasia de células de Leydig. La terapia con testosterona disminuyó la LH y los nódulos inesperadamente desaparecieron. En dos ocasiones, al interrumpir esta terapia, la LH aumentó y los nódulos reaparecieron. Este proceso revirtió nuevamente con el uso de testosterona, sugiriendo una hiperplasia de células de Leydig dependiente del estímulo crónico de LH.

Role of testosterone to estradiol ratio in predicting the efficacy of recombinant human chorionic gonadotropin and testosterone treatment in male hypogonadism

ABSTRACT Objective: We aimed to investigate the role of testosterone to estradiol ratio in predicting the effectiveness of human chorionic gonadotropin and testosterone treatments in male hypogonadism. Materials and methods: Thirty-six male patients with hypogonadotropic hypogonadism were included in the study. Seventeen (47.2%) patients received weekly recombinant human choriogonadotropin alpha (hCG) treatment (group-1) and 19 (52.8%) received testosterone replacement therapy (T treatment) every 21 days (group-2). Under these treatments, adequate frequency of morning erection (≥3/week), testosterone to estradiol ratio (T/E), and testicular volume changes were analyzed. Results: The mean age of the patients was 28.5 ± 8.7 years. When the frequency of morning erection (≥3/week) was specified as adequate, the cut-off value for effective T/E ratio was found to be 12.0 (sensitivity 93.8%, specificity 90.0%). There was no significant difference between the treatment groups in terms of total testosterone levels, T/E ratio, or frequency of morning erections (≥3/week) (p > 0.05). However, there was a statistically significant difference between the groups in terms of median left-right testicular volume in favor of group-1 (p < 0,05). Conclusion: In patients with hypogonadism who are under treatment, elevated estradiol-induced erectile dysfunction symptoms may persist even if serum testosterone levels are normal. Testosterone to estradiol ratio can be used as a predictive value in the effective treatment of hypogonadotropic hypogonadism with hCG and T.

Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism / 中华医学杂志(英文版)

BACKGROUND@#Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH.@*METHODS@#Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance).@*RESULTS@#Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P  0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference.@*CONCLUSIONS@#The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Human chorionic gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL

ABSTRACT Purpose The 2018 American Urological Association guidelines on the Evaluation and Management of Testosterone Deficiency recommended that 300 ng/dL be used as the threshold for prescribing testosterone replacement therapy (TRT). However, it is not uncommon for men to present with signs and symptoms of testosterone deficiency, despite having testosterone levels greater than 300 ng/dL. There exists scant literature regarding the use of hCG monotherapy for the treatment of hypogonadism in men not interested in fertility. We sought to evaluate serum testosterone response and duration of therapy of hCG monotherapy for men with symptoms of hypogonadism, but total testosterone levels > 300 ng/dL. Materials and Methods We performed a multi-institutional retrospective case series of men receiving hCG monotherapy for symptomatic hypogonadism. We evaluated patient age, treatment indication, hCG dosage, past medical history, physical exam findings and serum testosterone and gonadotropins before and after therapy. Descriptive analysis was performed and Mann Whitney U Test was utilized for statistical analysis. Results Of the 20 men included in the study, treatment indications included low libido (45%), lack of energy (50%), and erectile dysfunction (45%). Mean testosterone improved by 49.9% from a baseline of 362 ng/dL (SD 158) to 519.8 ng/dL (SD 265.6), (p=0.006). Median duration of therapy was 8 months (SD 5 months). Fifty percent of patients reported symptom improvement. Conclusions Treatment of hypogonadal symptoms with hCG for men who have a baseline testosterone level > 300 ng/dL appears to be safe and efficacious with no adverse events.

Should human chorionic gonadotropine treatment increase thyroid volume?

Objective Our aim was to investigate the thyroid function tests and thyroid volume differences among males with isolated hypogonadotropic hypogonadism (IHH) who take androgen replacement treatment (ART). Materials and methods Forty-four male with IHH with a mean age 33.2 (18-54), diagnosed in Endocrinology and Metabolism Department between September 2013 and September 2014 and 40 healthy male control with a mean age 27.77 (18-55) were involved to study. Patient group was divided to testosterone-treated patients (n = 19) and human chorionic gonadotropine (hCG)-treated patients (n = 25). Patient group was compared in terms of total testosterone, thyroid function tests [thyroid stimulating hormone (TSH), free thyroxine (fT4)] and thyroid volume, before and 6 months after treatment. Patient group was compared with control group as well. Results When we compared the patient group with the control group, there was no significant difference for age, Body mass index, TSH, fT4 and thyroid volume between two groups before treatment. There was no difference in terms of TSH, but fT4, testosterone levels and thyroid volume were significantly higher after treatment, when the patient group was compared before and after treatment (p < 0.05). When we compared testosterone-treated patients and hCG-treated patients; thyroid volume was higher among hCG-treated patients (p = 0.001) but there was no difference for thyroid volume before and after testosterone treatment (p > 0.05). There was no statistically significant correlation between testosterone levels with TSH, fT4 and thyroid volume (r = 0.09, p = 0.32; r = 0.14, p = 0.11; r = 0.15, p = 0.09, respectively). Conclusion Our study showed that ART increases the thyroid volume especially in hCG-treated patients. Therefore, we suggest that thyroid volume changes should be followed up in hCG-treated patients.

Clinical Practice Guidance for the Use Of Clomiphene Citrate in Male Hormone Replacement Therapy (HRT).

Introduction: Inhibition of pituitary gonadotropin secretion in men by testosterone (T) is principally mediated by aromatization to estrogen (E), which inhibits hypothalamic secretion of gonadotropin-releasing hormone (GnRH). Material and Methods: Longitudinal clinical investigation unit-based evaluation of the clinical and biochemical response to E-receptor blockade. Initial monotherapy with 50 mg of clomiphene citrate (CC) daily for a period of 9 months, with diurnal morning peak testosterone and luteinizing hormone (LH) levels evaluated at three-month intervals thereafter. Th e patient then resumed hormone replacement therapy (HRT) using T cream with adjuvant CC therapy. Main Outcome Measures were Baseline and stimulated T and LH levels; eff ect on sexual function. Result(S): CC therapy resulted in complete normalization of pulsatile gonadotropin secretion, serum T level, and sexual function. Conclusion(S): Isolated hypogonadotropic hypogonadism (IHH) may result from an acquired defect of enhanced hypothalamic sensitivity to E-mediated negative feedback. Whereas direct T replacement therapy can further suppress endogenous gonadotropin secretion, treating IHH men with gonadotropins can stimulate endogenous T secretion and enhance fertility potential. Reversal of gonadotropin defi ciency with CC was found to have a similar biological eff ect.

Mild adrenal insufficiency due to a NROB1 (DAX1) gene mutation in a boy presenting an association of hypogonadotropic hypogonadism, reduced final height and attention deficit disorder / Insuficiência adrenal leve causada por mutação do gene NR0B1 (DAX1) em menino com uma associação de hipogonadismo hipogonadotrófico, baixa estatura final e transtorno de déficit de atenção

Mutation on NROB1 (DAX1) gene can cause different phenotypes of adrenal insufficiency in infancy. Long-term evolution of these patients shows that it is possible to have an association with hypogonadotropic hypogonadism. In this article we describe the evolution of a patient with NROB1 gene mutation, diagnosed with a mild form of adrenal insufficiency, and we highlight the presence of hypogonadotropic hypogonadism and short stature, besides the presence of attention deficit disorder. Such associations should make physicians aware during the follow-up of patients with this disease.

Mutações no gene NROB1 (DAX1) podem levar a quadros de insuficiência adrenal com diferentes formas de apresentação na infância. A evolução a longo prazo desses pacientes mostra que pode haver associação com hipogonadismo hipogonadotrófico. Neste artigo, relatamos a evolução de um paciente com uma mutação do gene NROB1, diagnosticado com uma forma leve de insuficiência adrenal, na qual chamamos a atenção para a evolução com hipogonadismo hipogonadotrófico e baixa estatura final, além de apresentar transtorno de déficit de atenção. Tais associações devem ser motivo de atenção para os médicos no seguimento de pacientes portadores dessa alteração.

Medical management of non-obstructive azoospermia

Non-obstructive azoospermia is diagnosed in approximately 10% of infertile men. It represents a failure of spermatogenesis within the testis and, from a management standpoint, is due to either a lack of appropriate stimulation by gonadotropins or an intrinsic testicular impairment. The former category of patients has hypogonadotropic hypogonadism and benefits from specific hormonal therapy. These men show a remarkable recovery of spermatogenic function with exogenously administered gonadotropins or gonadotropin-releasing hormone. This category of patients also includes some individuals whose spermatogenic potential has been suppressed by excess androgens or steroids, and they also benefit from medical management. The other, larger category of non-obstructive azoospermia consists of men with an intrinsic testicular impairment where empirical medical therapy yields little benefit. The primary role of medical management in these men is to improve the quantity and quality of sperm retrieved from their testis for in vitro fertilization. Gonadotropins and aromatase inhibitors show promise in achieving this end point.

Growth after Hematopoietic Stem Cell Transplantation in Children with Acute Myeloid Leukemia

Previous studies have shown that hematopoietic stem cell transplantation (HSCT) may result in growth impairment. The purpose of this study was to evaluate the growth during 5 yr after HSCT and to determine factors that influence final adult height (FAH). We retrospectively reviewed the medical records of acute myeloid leukemia (AML) patients who received HSCT. Among a total of 37 eligible patients, we selected 24 patients who began puberty at 5 yr after HSCT (Group 1) and 19 patients who reached FAH without relapse (Group 2). In Group 1, with younger age at HSCT, sex, steroid treatment, hypogonadism and hypothyroidism were not significantly associated with growth impairment 5 yr after HSCT. History of radiotherapy (RT) significantly impaired the 5 yr growth after HSCT. Chronic graft-versus-host disease (cGVHD) only temporarily impaired growth after HSCT. In Group 2, with younger age at HSCT, steroid treatment and hypogonadism did not significantly reduce FAH. History of RT significantly reduced FAH. Growth impairment after HSCT may occur in AML patients, but in patients without a history of RT, growth impairment seemed to be temporary and was mitigated by catch-up growth.

Reversible Infertility Associated with Testosterone Therapy for Symptomatic Hypogonadism in Infertile Couple

PURPOSE: Androgen replacement therapy has been shown to be safe and effective for most patients with testosterone deficiency. Male partners of infertile couples often report significantly poorer sexual activity and complain androgen deficiency symptoms. We report herein an adverse effect on fertility caused by misusage of androgen replacement therapy in infertile men with hypogonadal symptoms. MATERIALS AND METHODS: The study population consisted of 8 male patients referred from a local clinic for azoospermia or severe oligozoospermia between January 2008 and July 2011. After detailed evaluation at our andrology clinic, all patients were diagnosed with iatrogenic hypogonadism associated with external androgen replacement. We evaluated changes in semen parameters and serum hormone level, and fertility status. RESULTS: All patients had received multiple testosterone undecanoate (NebidoR) injections at local clinic due to androgen deficiency symptoms combined with lower serum testosterone level. The median duration of androgen replacement therapy prior to the development of azoospermia was 8 months (range: 4-12 months). After withdrawal of androgen therapy, sperm concentration and serum follicle-stimulating hormone level returned to normal range at a median 8.5 months (range: 7-10 months). CONCLUSION: Misusage of external androgen replacement therapy in infertile men with poor sexual function can cause temporary spermatogenic dysfunction, thus aggravating infertility.

Novel mutation in the gonadotropin-releasing hormone receptor (GNRHR) gene in a patient with normosmic isolated hypogonadotropic hypogonadism / Nova mutação no receptor do hormônio liberador de gonadotrofinas (GNRHR) em um paciente com hipogonadismo hipogonadotrófico isolado normósmico

We report a novel GNRHR mutation in a male with normosmic isolated hypogonadotropic hypogonadism (nIHH). The coding region of the GNRHR gene was amplified and sequenced. Three variants p.[Asn10Lys;Gln11Lys]; [Tyr283His] were identified in the GNRHR coding region in a male with sporadic complete nIHH. The three variants were absent in the controls (130 normal adults). Familial segregation showed that the previously described p.Asn10Lys and p.Gln11Lys are in the same allele, in compound heterozygozity with the novel variant p.Tyr283His. The p.[Asn10Lys;Gln11Lys] are known inactivating mutations. The p.Tyr283His affects a well-conserved residue, and in silico analysis suggested it is a deleterious variant. We describe a novel GNRHR mutation in a male with nIHH. Absence of the mutation in the control group, conservation among species, in silico analysis, and familial segregation suggest that p.Tyr283His, which was identified in compound heterozygozity with the p.[Asn10Lys;Gln11Lys] variants, is an inactivating mutation. Arq Bras Endocrinol Metab. 2012;56(8):540-4.

Relatamos uma nova mutação no gene GNRHR em um homem com hipogonadismo hipogonadotrófico isolado normósmico (HHIn). A região codificadora do gene GNRHR foi amplificada e sequenciada. Três variantes p.[Asn10Lys;Gln11Lys]; [Tyr283His] foram identificadas no GNRHR em um homem com HHIn esporádico. As três variantes estavam ausentes no grupo controle (130 adultos normais). A segregação familiar mostrou que as variantes previamente descritas p.[Asn10Lys;Gln11Lys] se localizavam no mesmo alelo, em heterozigose composta com a nova variante p.Tyr283His. As mutações p.[Asn10Lys;Gln11Lys] são sabidamente inativadoras. A variante p.Tyr283His afeta um resíduo bem conservado, e a análise in silico sugeriu que essa é uma mutação deletéria. Descrevemos uma mutação inédita no gene GNRHR em um paciente com HHIn nIHH. A ausência da variante no grupo controle, a conservação entre as espécies, a análise in silico e a segregação familiar sugerem que a p.Tyr283His é uma mutação inativadora, identificada em heterozigose composta com as mutações p.[Asn10Lys;Gln11Lys]. Arq Bras Endocrinol Metab. 2012;56(8):540-4.

Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study

INTRODUCTION: Male testosterone deficiency is associated with bad sexual function and quality of life (QoL). The aim of this study was to determine whether a daily dose of 25 mg clomiphene citrate (CC) is effective in stimulating the endogenous testosterone production pathway and to address the applicability of this medication as a therapeutic option for symptomatic hypogonadism. MATERIALS AND METHODS: This was a prospective study. Men with low sexual desire and testosterone levels (T) below 400 ng/dL were selected to receive CC. Blood samples were obtained to determine baseline measurements of serum T, estradiol, LH, lipid profile and fasting plasma glucose. Each patient was treated with a daily dose of 25 mg CC for at least 3 months. Patients were asked if they experienced any side effects related to the use of CC and if they experienced any improvement in their sexual profile. Paired samples T-test was utilized to analyze responses to therapy. RESULTS: Our cohort consisted of 125 men with hypogonadism and low libido. Mean age was 62 years (± 11.1 years). Serum T levels ranged from 309 ng/dL (baseline, mean value) to 642 ng/dL (3 months after CC initiation, mean value) (p < 0.001). Serum cholesterol levels ranged from 197 to 186 mg/dL (p = 0.003). There were no statistically significant differences when comparing pre and post-treatment HDL-Cholesterol, triglycerides, fasting plasma glucose and prolactin. All men reported improvements in the post-treatment QoL scores. No serious adverse events were recorded. CONCLUSIONS: The CC was effective in stimulating the endogenous production of testosterone. A lower level of total cholesterol was verified after three months of treatment. This medication should be considered as a therapeutic option for some patients with symptomatic male testosterone deficiency.

Inducción de la pubertad en el síndrome de Turner / Induction of puberty in Turner's syndrome

Turner's Syndrome is the most frequent cause of female hypogonadism. Puberty must be pharmacologically induced in over 80 percent of these girls. Induction must be completed in a manner closest to physiology as possible. It is recommended that this induction be initiated at age 12 y.o. with natural estrogens (17 beta estradiol) in low dosage, equivalent to 1/10 a 1/8 of substitution dose, increasing stepwise and adding, after two years, a progestin to generate a menstruation. This revision shows various proposed schemes, as well as therapeutic alternatives available in Chile.

El síndrome de Turner es la causa más frecuente de hipogonadismo femenino. La pubertad tiene que ser inducida farmacológicamente en más del 80 por ciento de estas niñas. Esta inducción debe hacerse de la forma más fisiológica posible. Se recomienda iniciar esta inducción a los 12 años de edad cronológica, con estrógenos naturales (17 beta estradiol) en dosis bajas, equivalentes a 1/10 a 1/8 de la dosis de sustitución, aumentando la dosis por peldaños y agregando luego de dos años una progestina cíclica para generar una menstruación. En esta revisión se muestran los diversos esquemas propuestos en la literatura así como las alternativas terapéuticas existentes en Chile.

Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas / Clomifeno não reverte o hipogonadismo na maioria dos homens com adenomas pituitários não funcionais tratados de forma convencional

OBJETIVE: To evaluate the effect of clomiphene in men with hypogonadism and conventionally treated nonfunctioning pituitary adenomas (NFPA). PATIENTS AND METHODS: Open label, single-arm, prospective trial. Nine hypogonadal men (testosterone < 300 ng/dL and low/normal LH) with previously treated NFPA. Clomiphene (50 mg/day orally) for 12 weeks. Testosterone, estradiol, LH, FSH, prolactin and erectile function were evaluated before and after 10 days, 4, 8 and 12 weeks of clomiphene treatment. RESULTS: After clomiphene treatment, testosterone and erectile function improved in only one patient. In the remaining eight patients, testosterone levels decreased whereas LH, FSH, and estradiol remained unchanged. Insulin sensitivity increased in unresponsive patients. CONCLUSIONS: Compared with hypogonadal men with prolactinomas under dopaminergic therapy, clomiphene treatment failed to restore normal testosterone levels in most patients with conventionally treated NFPA.

OBJETIVO: Avaliar o efeito do clomifeno em homens com hipogonadismo e adenoma hipofisário não funcionante (NFPA) previamente tratados. PACIENTES E MÉTODOS: Aberto, braço único, prospectivo. Nove homens hipogonádicos (testosterona < 300 ng/dL e LH normal/baixo) com NFPA previamente tratados. Clomifeno (50 mg/dia oral) por 12 semanas. Testosterona, estradiol, LH, FSH, prolactina e função erétil foram avaliados antes e após 10 dias, 4, 8 e 12 semanas de clomifeno. RESULTADOS: Após clomifeno, a testosterona e a função erétil melhoraram em um paciente. Em outros oito pacientes, os níveis de testosterona reduziram enquanto os níveis de LH, FSH, e estradiol permaneceram inalterados. A sensibilidade à insulina aumentou nos não respondedores. CONCLUSÕES: Em contraste com homens hipogonádicos com prolactinomas tratados com agonistas dopaminérgicos, a maioria dos hipogonádicos com NFPA falha em restaurar os níveis de testosterona durante o uso de clomifeno.

Câncer de próstata e testosterona: riscos e controvérsias: [revisão] / Prostate carcinoma and testosterone: risks and controversies: [review]

O hipogonadismo é uma síndrome clínica e bioquímica que pode estar associada a um prejuízo significativo na qualidade de vida (QoL) do homem. Com o aumento na expectativa de vida e sobrevida do câncer prostático (CaP), espera-se um número maior de diagnósticos de hipogonadismo em homens submetidos ao tratamento potencialmente curativo do CaP. Apesar da contraindicação clássica do emprego de terapia de reposição com testosterona (TRT) em homens com diagnóstico ou suspeita de CaP, não há evidência convincente de que a normalização dos níveis de testosterona séricos em homens com baixos níveis seja deletéria. Em poucas séries de casos que descreveram a TRT após o tratamento do CaP, não houve casos de progressão clínica ou bioquímica do tumor. Não obstante a literatura seja limitada, os dados disponíveis sugerem que a TRT pode ser considerada em homens hipogonádicos selecionados, previamente tratados curativamente para o CaP de baixo risco e sem evidência de doença ativa.

Hypogonadism is a clinical and biochemical syndrome which may cause significant detriment in the quality of life. With the increase in life expectancy and prostate cancer survival a significant increase in the number of men with hypogonadism who have undergone presumably curative treatment for PCa is anticipated. Despite the widespread contraindication of testosterone in men with known or suspected prostate cancer, there is no convincing evidence that the normalization of testosterone serum levels in men with low, but not castrate levels, is deleterious. Although further studies are necessary before definitive conclusions can be drawn, the available evidence suggests that testosterone replacement therapy can be cautiously considered in selected hypogonadal men treated with curative intent for low risk prostate cancer and without evidence of active disease.

Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids: [revisão] / Gonadotrophic axis dysfunction in men with HIV-infection/Aids: [review]

A disfunção do eixo gonadotrófico é frequentemente observada em pacientes infectados pelo HIV. A patogênese é multifatorial e está relacionada à duração da infecção pelo HIV, aos efeitos citopáticos diretos do vírus, ao uso de drogas gonadotóxicas, às infecções oportunistas, às neoplasias, à desnutrição, entre outros fatores. Em homens, a redução dos níveis de testosterona está associada à perda de massa e de força muscular, à redução da densidade mineral óssea, à lipodistrofia, à depressão, à astenia, à fadiga e à disfunção sexual. Em pacientes infectados pelo HIV com hipogonadismo, inúmeros estudos têm comprovado os efeitos benéficos da reposição de testosterona sobre o perfil metabólico e a distribuição da gordura corporal, com aumento da massa corporal magra, além de promover melhora da qualidade de vida, reduzir a perda de massa óssea e reduzir os índices de depressão. Assim, esta revisão teve como objetivo trazer uma breve atualização sobre o presente tema, abordando dados epidemiológicos, mecanismos fisiopatológicos e estratégias terapêuticas para as principais anormalidades do eixo gonadotrófico masculino associadas à infecção pelo HIV e ao seu tratamento.

Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.

Evaluation of late-onset hypogonadism (andropause) treatment using three different formulations of injectable testosterone / Avaliação do tratamento de pacientes hipogonádicos tardios (andropausa) usando três formulações diferentes de testosterona injetável

OBJECTIVE: To compare the modalities of treatment for male hypogonadism available in Brazil. METHODS: Thirty-two men with late-onset hypogonadism ("andropause") were followed-up in the Hospital de Guarnição de Florianópolis, in Florianópolis, south Brazil. Clinical diagnosis was established according to AMS questionnaire (positive if equal to or higher than 27 points), and laboratorial diagnosis was made through low values of total testosterone (under 300 ng/dL) and/or free calculated testosterone (under 6.5 ng/dL). Patients were randomized to three non-enteral treatment groups (Deposteron® - 11 patients; Durateston® - 11 patients; and Nebido® - 10 patients). RESULTS: Clinically, Nebido® seemed to be superior when compared to Deposteron® (mean value of improvement percentage; p = 0.03) and when compared to Durateston® (post-treatment average AMS score; p = 0.03). According to laboratorial analysis, Nebido® showed higher testosterone levels than Deposteron® and Durateston® (p < 0.001). CONCLUSIONS: All non-enteral testosterone formulas available in the Brazilian market are efficient in raising testosterone levels and in clinical improvement of hypogonadal patients. Nebido® showed both a better clinical and laboratorial effectiveness.

OBJETIVO: Comparar os tratamentos para hipogonadismo masculino disponíveis no Brasil. MÉTODOS: Foram selecionados 32 homens com hipogonadismo tardio ("andropausa") no Hospital de Guarnição de Florianópolis. O diagnóstico foi feito por meio do questionário AMS (acima de 27 pontos) e dos níveis diminuídos de testosterona total dosada (abaixo de 300 ng/dL) e/ou testosterona livre calculada (abaixo de 6,5 ng/dL). Os pacientes foram divididos em três grupos de tratamento parenteral (Deposteron® - 11 pacientes; Durateston® - 11 pacientes; Nebido® - 10 pacientes). RESULTADOS: Clinicamente, o tratamento com Nebido® mostrou-se superior ao tratamento com Deposteron® (média do percentual de melhora; p = 0,03) e ao Durateston® (média do questionário AMS pós-tratamento; p = 0,03). Laboratorialmente, o tratamento com Nebido® mostrou níveis de testosterona superiores ao Deposteron® e Durateston® (p < 0,001). CONCLUSÕES: As três formulações de testosterona parenteral existentes no mercado brasileiro são eficientes em elevar os níveis de testosterona e melhorar clinicamente pacientes hipogonádicos, sendo o Nebido® mais efetivo clínica e laboratorialmente.